| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2014: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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| Outline of Final Research Achievements |
Skeletal muscle has a pleiotropic role in organismal energy metabolism by storing protein as an energy source, or by excreting endocrine hormones. Muscle proteolysis is tightly controlled by the hypothalamus-pituitary-adrenal signalling axis via a glucocorticoid-driven transcriptional programme. We unraveled the physiological significance of this catabolic process using skeletal muscle-specific glucocorticoid receptor (GR) knockout (GRmKO) mice. These mice have increased muscle mass but smaller adipose tissues.
Metabolically, GRmKO mice show a drastic shift of energy utilization and storage in muscle, liver and adipose tissues. The resulting depletion of plasma alanine serves as a cue to increase plasma levels of FGF21 and activates liver-fat communication, leading to the activation of lipolytic genes in adipose tissues. This skeletal muscle-liver-fat signalling axis may serve as a target for the
development of therapies against various metabolic diseases, including obesity.
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